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Title: SU-F-R-01: Preclinical Radioimmunogenomics Study to Design Personalized Radiotherapy

Abstract

Purpose: Radiogenomics is an active area of research to find clinical correlation between genomics and radiotherapy outcomes. In this era, many different biological issues should be taken into account. In this study we aimed to introduce “Radioimmunogenomics” as a new approach to study immunogetics issue regard to radiotherapy induced clinical manifestations. Methods: We studied different immunological pathways and signaling molecules which underling radiation response of normal and malignant tissues. In the other hand, we found many genes and proteins are responsible to radiation effects on biological tissues. We defined a theoretical framework to correlate these genes with radiotherapy outcomes as TCP and NTCP biological dose tools. Results: Our theoretical results showed, high-throughput immunogenomics biomarkers can be correlated with radiotherapy outcomes. Genes regarding to inflammation, apoptosis, repair molecules and many other immunological markers can be defined as radioimmune markers to predict radiotherapy response. Conclusion: Radioimmunogenomics can be used as a new personalized radiotherapy research area to enhance treatment outcome as well as quality of life.

Authors:
 [1]
  1. Iran University of Medical Sciences, Tehran, Iran, Tehran, Tehran (Iran, Islamic Republic of)
Publication Date:
OSTI Identifier:
22626731
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; ANIMAL TISSUES; APOPTOSIS; BIOLOGICAL MARKERS; BIOLOGICAL RADIATION EFFECTS; BIOLOGICAL REPAIR; CORRELATIONS; GENES; INFLAMMATION; MOLECULES; PROTEINS; RADIATION DOSES; RADIOTHERAPY; STANDARD OF LIVING; TCP

Citation Formats

Abdollahi, H. SU-F-R-01: Preclinical Radioimmunogenomics Study to Design Personalized Radiotherapy. United States: N. p., 2016. Web. doi:10.1118/1.4955773.
Abdollahi, H. SU-F-R-01: Preclinical Radioimmunogenomics Study to Design Personalized Radiotherapy. United States. doi:10.1118/1.4955773.
Abdollahi, H. Wed . "SU-F-R-01: Preclinical Radioimmunogenomics Study to Design Personalized Radiotherapy". United States. doi:10.1118/1.4955773.
@article{osti_22626731,
title = {SU-F-R-01: Preclinical Radioimmunogenomics Study to Design Personalized Radiotherapy},
author = {Abdollahi, H},
abstractNote = {Purpose: Radiogenomics is an active area of research to find clinical correlation between genomics and radiotherapy outcomes. In this era, many different biological issues should be taken into account. In this study we aimed to introduce “Radioimmunogenomics” as a new approach to study immunogetics issue regard to radiotherapy induced clinical manifestations. Methods: We studied different immunological pathways and signaling molecules which underling radiation response of normal and malignant tissues. In the other hand, we found many genes and proteins are responsible to radiation effects on biological tissues. We defined a theoretical framework to correlate these genes with radiotherapy outcomes as TCP and NTCP biological dose tools. Results: Our theoretical results showed, high-throughput immunogenomics biomarkers can be correlated with radiotherapy outcomes. Genes regarding to inflammation, apoptosis, repair molecules and many other immunological markers can be defined as radioimmune markers to predict radiotherapy response. Conclusion: Radioimmunogenomics can be used as a new personalized radiotherapy research area to enhance treatment outcome as well as quality of life.},
doi = {10.1118/1.4955773},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}
  • Purpose: To compare three different pharmacokinetic models for analysis of dynamic-contrast-enhanced (DCE)-CT data with respect to different acquisition times and location of region of interest. Methods: Eight rectal cancer patients with pre-treatment DCE-CTs were included. The dynamic sequence started 4–10seconds(s) after the injection of contrast agent. The scan included a 110s acquisition with intervals of 40×1s+15×3s+4×6s. An experienced oncologist outlined the tumor region. Hotspots with top-5%-enhancement were also identified. Pharmacokinetic analysis was performed using three different models: deconvolution method, Patlak model, and modified Toft’s model. Perfusion parameters as blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface-area-product (PS),more » volume transfer constant (Ktrans), and flux rate constant (Kep), were compared with respect to different acquisition times of 45s, 65s, 85s and 105s. Both hotspot and whole-volume variances were also assessed. The differences were compared using the Wilcoxon matched-pairs test and Bland-Altman plots. Results: Moderate correlation was observed for various perfusion parameters (r=0.56–0.72, p<0.0001) but the Wilcoxon test revealed a significant difference among the three models (P < .001). Significant differences in PS were noted between acquisitions of 45s versus longer time of 85s or 105s (p<0.05) using Patlak but not with the deconvolution method. In addition, measurements varied substantially between whole-volume vs. hotspot analysis. Conclusion: The radiation dose of DCE-CT was on average 1.5 times of an abdomen/pelvic CT, which is not insubstantial. To take the DCE-CT forward as a biomarker in oncology, prospective studies should be carefully designed with the optimal image acquisition and analysis technique. Our study suggested that: (1) different kinetic models are not interchangeable; (2) a 45s acquisition might not be sufficient for reliable permeability measurement in rectal cancer using Patlak model, but might be achievable using deconvolution method; and (3) local variations existed inside the tumor, and both whole-volume-averaged and local-heterogeneity analysis is recommended for future quantitative studies. This work is supported by the National High-tech R&D program for Young Scientists by the Ministry of Science and Technology of China (Grant No. 2015AA020917), Natural Science Foundation of China (NSFC Grant No. 81201091).« less
  • Purpose: Small animal irradiation can provide preclinical insights necessary for clinical advancement. In order to provide clinically relevant data, these small animal irradiations must be designed such that the treatment methods and results are comparable to clinical protocols, regardless of variations in treatment size and modality. Methods: Small animal treatments for four treatment sites (brain, liver, lung and spine) were investigated, accounting for change in treatment energy and target size. Up to five orthovoltage (300kVp) beams were used in the preclinical treatments, using circular, square, and conformal tungsten apertures, based on the treatment site. Treatments were delivered using the imagemore » guided micro irradiator (microIGRT). The plans were delivered to a mouse sized phantom and dose measurements in axial and coronal planes were performed using radiochromic film. The results of the clinical and preclinical protocols were characterized in terms of conformality number, CTV coverage, dose nonuniformity ratio, and organ at risk sparing. Results: Preclinical small animal treatment conformality was within 1–16% of clinical results for all treatment sites. The volume of the CTV receiving 100% of the prescription dose was typically within 10% of clinical values. The dose non-uniformity was consistently higher for preclinical treatments compared to clinical treatments, indicating hot spots in the target. The ratios of the mean dose in the target to the mean dose in an organ at risk were comparable if not better for preclinical versus clinical treatments. Finally, QUANTEC dose constraints were applied and the recommended morbidity limits were satisfied in each small animal treatment site. Conclusion: We have shown that for four treatment sites, preclinical 3D conformal small animal treatments can be clinically comparable if clinical protocols are followed. Using clinical protocols as the standard, preclinical irradiation methods can be altered and iteratively improved to achieve a clinically relevant irradiation model.« less
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  • Purpose: The shape of the Positron Emission Tomography (PET) image represents the heterogeneity of tumor growth in various directions, and thus could be associated with tumor malignancy. We have proposed a median geodesic distance (MGD) to represent the local complexity of the shape and use a normalized MGD (NMGD) to quantify the shape, and found a potential correlation of NMGD to survival in a 20-patient pilot study. This study was to verify the finding in a larger patient cohort. Methods: Geodesic distance of two vertices on a surface is defined as the shortest path on the surface connecting the twomore » vertices. The MGD was calculated for each vertex on the surface to display the local complexity of the shape. The NMGD was determined as: NMGD = 100*standard deviation(MGDs)/mean(MGDs). We applied the NMGD to 40 NSCLC patients who were enrolled in prospective PET image protocols and received radiotherapy. Each patient had a pre-treatment PET scan with the resolution of 4mm*4mm*5mm. Tumors were contoured by a professional radiation oncologist and triangulation meshes were built up based on the contours. Results: The mean and standard deviation of NMGD was 6.4±3.0. The OS was 33.1±16.9 months for low NMGD group, and 15.4±15.6 months for the high NMGD group. The low NMGD group had significant better OS than the high NMGD group (p=0.0013). Conclusion: NMGD could be used as a shape biomarker to predict survival and the MGD could be combined with image texture in future to increase prediction accuracy. This study was supported by Award Number 1R01CA166948 from the NIH and National Cancer Institute.« less
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